An infectious agent isolated from synovial cells of a patient with rheumatoid arthritis (RA), by long-term cocultivation and passage in suckling mice has been tentatively identified as a parvovirus. This isolate has a distinctive pathology for murine species, has morphological characteristics of the parvorviruses, and its physical-chemical properties also suggest membership in that virus group. The organism is now designated RA-1. More than 40 cell lines tested thus far have failed to produce significant titers of infectious RA-1, but now one cell line (CFK, feline kidney) produces significant amounts of viral antigen when infected with RA-1 extracted from mouse brain. Rabbit antisera to RA-1 neutralize its infectivity for mice, to high dilutions. Additional isolates from 6 other patients with RA have yielded agents which are infectious for the mice, yielding symptoms associated with RA-1 infection. Data obtained in the enzyme-linked immunosorbent assay (ELISA) show that these 6 later isolates share one or more antigens with the RA-1 virus. Another 6 patient's synovial cell cultures were harvested and used to infect the CFK cells directly. Degenerative joint disease control cultures were handled in an identical way. Antigen was harvested from the RA-infected CFK cells which is also cross-reactive with RA-1 by ELISA. Therefore an additional 12 patients' synovial cells have yield cross-reactive antigen by two different methods, one not involving mice. Morphologically similar particles have also been found by an investigator in London, from 7 of 10 RA synovial menbranes, but none in osteoarthritic and sarcoid controls. These samples were brought to our lab by Dr. Stierle, and 5/7 show cross-reactivity with RA-1 by ELISA. This proposal is designed to investigate the relationship of RA-1 and other isolates to the pathophysiology and/or etiology of RA. This will be done by: examination of additional RA materials and controls for presence of virus; production of polyclonal and monoclonal antibodies for examination of antigen presence in RA tissues and other connective tissue disease; serological studies against RA-1; final characterization of RA-1 as a parvovirus; and further study of the relationship of RA-1 to other human and mammalian parvoviruses.